... adults with type 2 diabetes who take insulin in addition to the recommended first-line drug therapy, metformin, had a 30 percent higher risk of heart attack, stroke or death when compared to similar patients who instead augment their metformin regimen with a sulfonylurea.

New heart attacks and strokes occurred at similar rates in both groups but death (from all causes) was 44 percent higher in patients who added insulin compared to those who added a sulfonylurea.

... type 2 ... Diet and exercise often provide an effective first-line intervention for this disease, but many patients require a medication, and metformin is recommended as a first-line treatment. Many patients eventually require additional medicines, and according to Roumie the choice of a second medication has been less clear.

"A couple of small clinical trials have shown that using insulin earlier in a disease course helps preserve beta cells in your pancreas longer," she said. On the other hand, "multiple large clinical trials have found either no benefit or potential harm from attempting very tight management of glucose. We wanted to look within a real-world practice at the drugs that patients use and evaluate the outcomes."

In a statement accompanying the study, Roumie wrote, "Although adding insulin seems a reasonable option for some patients who have very high glucose or who desire flexible and fast blood sugar control, the study findings suggest that for most patients who need a second diabetes drug, adding a sulfonylurea to metformin should be preferred to adding insulin."

At present, any underlying mechanism that might explain the increased risk of death found in the study remains unknown. [emphasis mine]